As a result of the healing process that follows surgery, complications frequently arise due to the natural tendency of the body to form adhesions. Postsurgical adhesions negatively impact patient comfort and organ function.3-5 Post-surgical adhesions are particularly problematic for cardiac surgery patients. Many patients that have cardiac surgery, especially pediatric patients, must undergo reoperative procedures during their lifetime.6-8 The presence of postsurgical cardiac adhesions increases the difficulty and risks of the reoperative procedure due to increased surgery times and potential hemorrhaging upon gaining re-access to the heart.8 
Two main approaches exist for reducing or attempting to prevent cardiac adhesions: pharmacological therapy and physical barriers. Drugs that prevent or reverse adhesion processes disrupt biochemical pathways of inflammation and fibrin deposition (see e.g., WO 2013135647 A1). Unfortunately, these processes are also vital for wound healing. Achieving adequate drug concentration at the site of action, especially for ischemic tissues, is also challenging.
A more viable approach is the use of a physical barrier after surgery to prevent fusion of the heart to surrounding tissues. The barriers can be either preformed membranes (see e.g., US 20120088832 A1, CA 2513640 C, and WO 2013032201 A2) or injectable hydrogels (fast gelling liquids) (see e.g., EP 1967220 A2, EP 2470223 A2 and U.S. Pat. No. 5,874,500 A). Preformed anti-adhesive materials need to be cut before application to the tissue, and must be sutured into place to prevent slippage. Injectable hydrogels allow the freedom of applying material where needed by “painting” or spraying the precursor components and are capable of quickly forming a protective gel over the surface of the tissue. Therefore, a promising method to prevent postsurgical adhesions is to coat the tissue with a fast gelling polymer to prevent the susceptible tissue from adhering to other nearby tissue organs.3 
Materials that bind to tissues are widely used in clinical procedures; including abdominal, brain, spine, and cardiac surgeries. These materials are used to achieve homeostasis, seal tissues, deliver exogenous substances locally, or prevent postsurgical adhesions. The safety and efficacy of these materials is directly impacted by the purity of the components and mode of material formation.1, 2 For synthetic materials, the cross-linking chemistry and subsequent degradation products can dramatically impact the biocompatibility of the material.1 There are, however, only a limited number of materials that prevent postsurgical adhesions in a clinical setting. Further, while a variety of different materials have been investigated in animals and humans, no materials to date, have been capable of preventing adhesion formation post-cardiac surgery.
The mechanism of material adherence to tissue can be divided into two modes, non-covalent and covalent. Non-covalent materials include collagen, fibrin, and gelatin as well as ionic and thermoresponsive polymers. While these materials generally exhibit good biocompatibility, they are rapidly degraded or removed from the tissue surface in vivo due to the non-covalent association. Additionally, the protein-based materials contain ligands that promote cellular attachment, which is not ideal for preventing postsurgical adhesions that are the result of inflammation.3, 9 
Covalent attachment can be achieved through two different approaches. One approach uses radical polymerization or anionic polymerization (cyanoacrylates). However, due to the polymerizable functional groups these systems have exhibited toxicity in vivo.1, 10 The other covalent approach relies on reaction with nucleophilic functional groups present on the tissue surface by using epoxides, activated carboxylic acids, or aldehydes. This approach is attractive since the materials can be synthesized with a desired number of functional groups and molecular weights to tune tissue reactivity, gelation times, and facilitate clearance from the body upon degradation.1 
From a chemistry perspective, adhesion prevention is challenging, especially in a cardiac surgery setting. The material should be easily applied, gel rapidly (<5 min) on the wet tissue surface, remain on the tissue for at least 2 weeks to overcome the initial inflammatory response post-surgery, exhibit minimal swelling (to not impede cardiac function), and be biocompatible. This means that the pre-gel materials must be capable of reacting quickly and efficiently with themselves as well as with tissue, and the cross-linking functional groups must be biocompatible. Once gelled, the material must prevent cellular adhesion to prevent fibrin deposition from infiltrating cells, since this leads to adhesions.3 
Oxime chemistry has been successfully used in a variety of in vitro and in vivo applications,11 and PEG-coated surfaces have shown to minimize protein adsorption12 and cellular adhesion.13 It has been demonstrated that oxime chemistry is biocompatible, chemospecific, and bioorthogonal.11, 14 
Therefore, what are needed are improved methods and compositions for use as an anti-adhesion barrier. It would be desirable to employ a new chemistry that results in rapid forming hydrogels capable of adhering to tissue surfaces. The present invention addresses these and other related needs in the art.